MX2015000426A - Incremento de actividad de celulas t car mediante cointroduccion de un anticuerpo biespecifico. - Google Patents
Incremento de actividad de celulas t car mediante cointroduccion de un anticuerpo biespecifico.Info
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- MX2015000426A MX2015000426A MX2015000426A MX2015000426A MX2015000426A MX 2015000426 A MX2015000426 A MX 2015000426A MX 2015000426 A MX2015000426 A MX 2015000426A MX 2015000426 A MX2015000426 A MX 2015000426A MX 2015000426 A MX2015000426 A MX 2015000426A
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Families Citing this family (122)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105358576B (zh) | 2013-02-20 | 2020-05-05 | 诺华股份有限公司 | 使用人源化抗EGFRvIII嵌合抗原受体治疗癌症 |
EP2958942B1 (en) | 2013-02-20 | 2020-06-03 | Novartis AG | Effective targeting of primary human leukemia using anti-cd123 chimeric antigen receptor engineered t cells |
CA2904230A1 (en) * | 2013-03-05 | 2014-09-12 | Baylor College Of Medicine | Engager cells for immunotherapy |
US9745368B2 (en) | 2013-03-15 | 2017-08-29 | The Trustees Of The University Of Pennsylvania | Targeting cytotoxic cells with chimeric receptors for adoptive immunotherapy |
UY35468A (es) * | 2013-03-16 | 2014-10-31 | Novartis Ag | Tratamiento de cáncer utilizando un receptor quimérico de antígeno anti-cd19 |
ES2645393T3 (es) | 2013-05-29 | 2017-12-05 | Cellectis | Métodos de manipulación de linfocitos T para inmunoterapia usando el sistema de nucleasa Cas guiada por ARN |
CA2931684C (en) | 2013-12-19 | 2024-02-20 | Novartis Ag | Human mesothelin chimeric antigen receptors and uses thereof |
US10287354B2 (en) | 2013-12-20 | 2019-05-14 | Novartis Ag | Regulatable chimeric antigen receptor |
US11028143B2 (en) | 2014-01-21 | 2021-06-08 | Novartis Ag | Enhanced antigen presenting ability of RNA CAR T cells by co-introduction of costimulatory molecules |
WO2015120187A1 (en) * | 2014-02-05 | 2015-08-13 | The University Of Chicago | Chimeric antigen receptors recognizing cancer-spevific tn glycopeptide variants |
AU2015213437B2 (en) * | 2014-02-07 | 2018-04-05 | Mcmaster University | Trifunctional T cell-antigen coupler and methods and uses thereof |
CN106029875A (zh) | 2014-02-14 | 2016-10-12 | 塞勒克提斯公司 | 为了靶向存在于免疫细胞和病理细胞两者上的抗原而工程化的免疫治疗细胞 |
KR102487608B1 (ko) | 2014-04-07 | 2023-01-12 | 노파르티스 아게 | 항-cd19 키메라 항원 수용체를 사용한 암의 치료 |
EP3169773B1 (en) | 2014-07-15 | 2023-07-12 | Juno Therapeutics, Inc. | Engineered cells for adoptive cell therapy |
CN112481283A (zh) | 2014-07-21 | 2021-03-12 | 诺华股份有限公司 | 使用cd33嵌合抗原受体治疗癌症 |
KR102612313B1 (ko) | 2014-07-21 | 2023-12-12 | 노파르티스 아게 | 인간화 항-bcma 키메라 항원 수용체를 사용한 암의 치료 |
US11542488B2 (en) | 2014-07-21 | 2023-01-03 | Novartis Ag | Sortase synthesized chimeric antigen receptors |
BR112017000939A2 (pt) | 2014-07-21 | 2017-11-14 | Novartis Ag | tratamento de câncer usando um receptor antigênico quimérico de cll-1 |
JP7084138B2 (ja) | 2014-08-19 | 2022-06-14 | ノバルティス アーゲー | 癌処置に使用するための抗cd123キメラ抗原受容体(car) |
CN114621969A (zh) | 2014-09-17 | 2022-06-14 | 诺华股份有限公司 | 用于过继免疫疗法的具有嵌合受体的靶向细胞毒性细胞 |
WO2016054520A2 (en) * | 2014-10-03 | 2016-04-07 | The California Institute For Biomedical Research | Engineered cell surface proteins and uses thereof |
AU2015330898B2 (en) | 2014-10-08 | 2022-03-10 | Novartis Ag | Biomarkers predictive of therapeutic responsiveness to chimeric antigen receptor therapy and uses thereof |
JP6625627B2 (ja) | 2014-10-14 | 2019-12-25 | ハロザイム インコーポレイテッド | アデノシンデアミナーゼ−2(ada2)、その変異体の組成物およびそれを使用する方法 |
CA2964948A1 (en) | 2014-10-31 | 2016-05-06 | The Trustees Of The University Of Pennsylvania | Altering gene expression in modified t cells and uses thereof |
JP7372728B2 (ja) * | 2014-10-31 | 2023-11-01 | ザ トラスティーズ オブ ザ ユニバーシティ オブ ペンシルバニア | 改変t細胞に関する方法および組成物 |
CA2969456A1 (en) | 2014-12-03 | 2016-06-09 | Juno Therapeutics, Inc. | Methods and compositions for adoptive cell therapy |
BR112017013176A2 (pt) * | 2014-12-19 | 2018-05-15 | Dana Farber Cancer Inst Inc | receptores de antígenos quiméricos e métodos para usá-los |
PL3560953T3 (pl) * | 2014-12-24 | 2024-05-13 | Autolus Limited | Komórka |
EP3240803B1 (en) | 2014-12-29 | 2021-11-24 | Novartis AG | Methods of making chimeric antigen receptor-expressing cells |
WO2016113203A1 (en) | 2015-01-12 | 2016-07-21 | Pieris Ag | Engineered t cells and uses therefor |
WO2016115482A1 (en) | 2015-01-16 | 2016-07-21 | Novartis Pharma Ag | Phosphoglycerate kinase 1 (pgk) promoters and methods of use for expressing chimeric antigen receptor |
CA2973525C (en) | 2015-01-26 | 2021-12-14 | Cellectis | Anti-cll1 specific single-chain chimeric antigen receptors (sccars) for cancer immunotherapy |
WO2016122738A1 (en) | 2015-01-31 | 2016-08-04 | The Trustees Of The University Of Pennsylvania | Compositions and methods for t cell delivery of therapeutic molecules |
WO2016126608A1 (en) | 2015-02-02 | 2016-08-11 | Novartis Ag | Car-expressing cells against multiple tumor antigens and uses thereof |
CN114958764A (zh) | 2015-04-08 | 2022-08-30 | 诺华股份有限公司 | Cd20疗法、cd22疗法和与cd19嵌合抗原受体(car)表达细胞的联合疗法 |
EP4234685A3 (en) | 2015-04-17 | 2023-09-06 | Novartis AG | Methods for improving the efficacy and expansion of chimeric antigen receptor-expressing cells |
CN105158466B (zh) * | 2015-05-05 | 2017-12-22 | 中国科学院广州生物医药与健康研究院 | 一种检测抗cd19的嵌合抗原受体t细胞对白血病细胞抑制作用的方法 |
IL255697B2 (en) | 2015-05-18 | 2023-11-01 | Tcr2 Therapeutics Inc | Compositions and methods for TCR programming using fusion proteins |
EP3307282A4 (en) * | 2015-06-12 | 2019-05-01 | Immunomedics, Inc. | TREATMENT OF DISEASES WITH CHIMERIC ANTIGEN RECEPTOR (CAR) AND T-CELL (T-CAR) OR NK (CAR-NK) CELL EXPRESSION CONSTRUCTIONS CAR CONSTRUCTIONS |
MA42902A (fr) * | 2015-07-08 | 2018-05-16 | Univ Johns Hopkins | Lymphocytes infiltrant la moelle (mil) en tant que source de lymphocytes t pour une thérapie par des récepteurs chimériques d'un antigène (car) |
MA42895A (fr) | 2015-07-15 | 2018-05-23 | Juno Therapeutics Inc | Cellules modifiées pour thérapie cellulaire adoptive |
CN108136008A (zh) * | 2015-07-15 | 2018-06-08 | 华盛顿大学 | 针对具有末端GlcNAcβ残基的肿瘤相关复合N-聚糖的抗体及其使用方法 |
SG10201912978PA (en) | 2015-07-21 | 2020-02-27 | Novartis Ag | Methods for improving the efficacy and expansion of immune cells |
US11667691B2 (en) | 2015-08-07 | 2023-06-06 | Novartis Ag | Treatment of cancer using chimeric CD3 receptor proteins |
KR20180041152A (ko) | 2015-08-11 | 2018-04-23 | 셀렉티스 | Cd38 항원 타겟팅 및 cd38 유전자 불활성화를 위하여 조작된 면역치료용 세포들 |
CN105384825B (zh) | 2015-08-11 | 2018-06-01 | 南京传奇生物科技有限公司 | 一种基于单域抗体的双特异性嵌合抗原受体及其应用 |
WO2017040195A1 (en) * | 2015-08-28 | 2017-03-09 | The Trustees Of The University Of Pennsylvania | Methods and compositions for cells expressing a chimeric intracellular signaling molecule |
WO2017040324A1 (en) * | 2015-08-28 | 2017-03-09 | The Trustees Of The University Of Pennsylvania | Methods and compositions for cells expressing a chimeric intracellular signaling molecule |
JP6905163B2 (ja) | 2015-09-03 | 2021-07-21 | ザ トラスティーズ オブ ザ ユニバーシティ オブ ペンシルバニア | サイトカイン放出症候群を予測するバイオマーカー |
SG10201913902RA (en) | 2015-10-13 | 2020-03-30 | Eureka Therapeutics Inc | Antibody agents specific for human cd19 and uses thereof |
RU2022103665A (ru) | 2015-10-23 | 2022-03-05 | Еурека Терапьютикс, Инк. | Химерные конструкции антитело/t-клеточный рецептор и их применения |
AU2016361451B2 (en) | 2015-11-27 | 2024-01-25 | Cartherics Pty. Ltd. | Genetically modified cells and uses thereof |
MA43380A (fr) * | 2015-12-03 | 2018-10-10 | Juno Therapeutics Inc | Récepteurs chimériques modifiés et compositions et procédés associés |
MA44140A (fr) | 2015-12-22 | 2021-05-19 | Dana Farber Cancer Inst Inc | Récepteur d'antigène chimérique (car) contre la mésothéline et anticorps contre l'inhibiteur de pd-l1 pour une utilisation combinée dans une thérapie anticancéreuse |
CN117025539A (zh) * | 2015-12-28 | 2023-11-10 | 诺华股份有限公司 | 制备嵌合抗原受体表达细胞的方法 |
US20200370011A1 (en) * | 2016-01-08 | 2020-11-26 | Prospect CharterCare RWMC, LLC d/b/a Roger Williams Medical Center | Geriatric car-t cells and uses thereof |
SG11201805872SA (en) * | 2016-01-21 | 2018-08-30 | Pfizer | Chimeric antigen receptors targeting epidermal growth factor receptor variant iii |
DK3405490T3 (da) | 2016-01-21 | 2022-01-10 | Pfizer | Mono- og bispecifikke antistoffer mod epidermal vækstfaktorreceptor variant iii og cd3 og anvendelser deraf |
GB201602974D0 (en) * | 2016-02-19 | 2016-04-06 | Clube Jasper R | Engineered cells & methods (1) |
WO2017165683A1 (en) * | 2016-03-23 | 2017-09-28 | Novartis Ag | Cell secreted minibodies and uses thereof |
US20190105348A1 (en) * | 2016-04-08 | 2019-04-11 | Unum Therapeutics Inc. | Chimeric receptors and uses thereof in immune therapy |
AU2017306432A1 (en) | 2016-08-02 | 2019-03-21 | TCR2 Therapeutics Inc. | Compositions and methods for TCR reprogramming using fusion proteins |
AR110676A1 (es) | 2016-10-07 | 2019-04-24 | Novartis Ag | Tratamiento del cáncer utilizando receptores de antígenos quiméricos |
BR112019007100A2 (pt) | 2016-10-07 | 2019-06-25 | Tcr2 Therapeutics Inc | composições e métodos para reprogramação de receptores de célula t com o uso de proteínas de fusão |
WO2018098365A2 (en) | 2016-11-22 | 2018-05-31 | TCR2 Therapeutics Inc. | Compositions and methods for tcr reprogramming using fusion proteins |
US11578115B2 (en) | 2017-01-10 | 2023-02-14 | The General Hospital Corporation | Chimeric antigen receptors based on alternative signal 1 domains |
EP4043485A1 (en) | 2017-01-26 | 2022-08-17 | Novartis AG | Cd28 compositions and methods for chimeric antigen receptor therapy |
AU2018219226A1 (en) | 2017-02-07 | 2019-08-15 | Seattle Children's Hospital (dba Seattle Children's Research Institute) | Phospholipid ether (PLE) CAR T cell tumor targeting (CTCT) agents |
CN110582288A (zh) | 2017-02-28 | 2019-12-17 | 恩多塞特公司 | 用于car t细胞疗法的组合物和方法 |
CN110461363B (zh) | 2017-03-16 | 2024-04-02 | 综合医院公司 | 靶向cd37的嵌合抗原受体 |
AU2018237159A1 (en) | 2017-03-22 | 2019-09-05 | Intellia Therapeutics, Inc. | Compositions and methods for immunooncology |
CN108727497A (zh) * | 2017-04-17 | 2018-11-02 | 沈阳美达博生物科技有限公司 | 一种cd19抗体及其应用 |
WO2018199593A1 (ko) * | 2017-04-24 | 2018-11-01 | 재단법인 목암생명과학연구소 | Her3 및 cd3에 결합하는 이중특이적 항체 |
CA3059755A1 (en) | 2017-04-26 | 2018-11-01 | Eureka Therapeutics, Inc. | Cells expressing chimeric activating receptors and chimeric stimulating receptors and uses thereof |
CN107267555B (zh) * | 2017-05-27 | 2020-03-20 | 上海优卡迪生物医药科技有限公司 | 一种基于octs技术的恶性胶质瘤car-t治疗载体及其构建方法和应用 |
PE20191847A1 (es) * | 2017-06-02 | 2019-12-31 | Pfizer | Receptores de antigenos quimericos que se dirigen a flt3 |
EP3645036A1 (en) | 2017-06-30 | 2020-05-06 | Cellectis | Cellular immunotherapy for repetitive administration |
WO2019032699A1 (en) * | 2017-08-09 | 2019-02-14 | Eureka Therapeutics, Inc. | CELLS EXPRESSING ANTIBODIES AND CELL SURFACE RECEPTORS |
CN109422815A (zh) * | 2017-08-28 | 2019-03-05 | 复旦大学 | 双特异性嵌合抗原受体c-Met/PD-1 scFv-CAR-T及其构建方法和应用 |
US20200230221A1 (en) | 2017-09-19 | 2020-07-23 | Massachusetts Institute Of Technology | Compositions for chimeric antigen receptor t cell therapy and uses thereof |
EP3694997A4 (en) | 2017-10-12 | 2021-06-30 | Mcmaster University | T-CELL ANTIGEN COUPLER WITH Y182T MUTATION, AND PROCEDURES AND USES THEREOF |
CN109706120A (zh) * | 2017-10-26 | 2019-05-03 | 深圳宾德生物技术有限公司 | 一种双靶点特异性t淋巴细胞及其制备方法和应用 |
JP7080514B2 (ja) * | 2017-12-22 | 2022-06-06 | アブクロン・インコーポレイテッド | 悪性b細胞を特異的に認知する抗体またはその抗原結合断片、これを含むキメラ抗原受容体及びその用途 |
CN109971717B (zh) * | 2017-12-28 | 2023-06-20 | 上海细胞治疗研究院 | 共表达cd40抗体与间皮素特异性嵌合抗原受体的t细胞及其用途 |
WO2019129850A1 (en) | 2017-12-29 | 2019-07-04 | Cellectis | Off-the-shelf engineered cells for therapy |
CN109988242A (zh) * | 2018-01-02 | 2019-07-09 | 武汉波睿达生物科技有限公司 | 联合嵌合抗原受体、表达载体、慢病毒及t细胞 |
CN108285486A (zh) * | 2018-01-15 | 2018-07-17 | 浙江阿思科力生物科技有限公司 | 以cd20为靶点的特异性抗体、car-nk细胞及其制备和应用 |
US11779602B2 (en) | 2018-01-22 | 2023-10-10 | Endocyte, Inc. | Methods of use for CAR T cells |
JP7462578B2 (ja) * | 2018-03-15 | 2024-04-05 | ファンダメンタル ソリューションズ コーポレーション | プログラム可能な免疫細胞受容体複合体システム |
CA3092355A1 (en) * | 2018-03-16 | 2019-09-19 | Cytoimmune Therapeutics, Inc. | Bispecific antibody car cell immunotherapy |
US10869888B2 (en) * | 2018-04-17 | 2020-12-22 | Innovative Cellular Therapeutics CO., LTD. | Modified cell expansion and uses thereof |
CN109161532A (zh) * | 2018-05-31 | 2019-01-08 | 华东师范大学 | 同时靶向psma和pd-l1的工程化免疫细胞 |
EP3806962A1 (en) | 2018-06-13 | 2021-04-21 | Novartis AG | Bcma chimeric antigen receptors and uses thereof |
US20210268027A1 (en) * | 2018-06-22 | 2021-09-02 | The General Hospital Corporation | Chimeric antigen receptors targeting cd37 and cd19 |
US11110123B2 (en) | 2018-07-17 | 2021-09-07 | Triumvira Immunologics Usa, Inc. | T cell-antigen coupler with various construct optimizations |
US10640562B2 (en) | 2018-07-17 | 2020-05-05 | Mcmaster University | T cell-antigen coupler with various construct optimizations |
SG11202100307WA (en) * | 2018-07-17 | 2021-02-25 | Triumvira Immunologics Usa Inc | T cell-antigen coupler with various construct optimizations |
CN110872356B (zh) * | 2018-09-03 | 2023-06-13 | 广西慧宝源健康产业有限公司 | 双特异性抗体及其使用方法 |
JP2022501067A (ja) * | 2018-09-26 | 2022-01-06 | 上海恒潤達生生物科技有限公司Hrain Biotechnology Co., Ltd. | Bcma及びcd19を標的とするキメラ抗原受容体、並びにその使用 |
CN112771071A (zh) | 2018-09-28 | 2021-05-07 | 麻省理工学院 | 胶原蛋白定位的免疫调节分子及其方法 |
WO2020092057A1 (en) | 2018-10-30 | 2020-05-07 | Yale University | Compositions and methods for rapid and modular generation of chimeric antigen receptor t cells |
CN109575143B (zh) * | 2018-12-29 | 2022-06-17 | 博生吉医药科技(苏州)有限公司 | 双特异性cd20-cd19-car及其应用 |
CN113766956B (zh) | 2019-03-05 | 2024-05-07 | 恩卡尔塔公司 | Cd19定向性嵌合抗原受体及其在免疫疗法中的用途 |
US11642409B2 (en) | 2019-06-26 | 2023-05-09 | Massachusetts Insttute of Technology | Immunomodulatory fusion protein-metal hydroxide complexes and methods thereof |
CN114729059A (zh) * | 2019-09-11 | 2022-07-08 | 宾夕法尼亚大学董事会 | 包含前列腺干细胞抗原(psca)嵌合抗原受体(cars)的组合物和方法 |
WO2021061648A1 (en) | 2019-09-23 | 2021-04-01 | Massachusetts Institute Of Technology | Methods and compositions for stimulation of endogenous t cell responses |
TW202134285A (zh) | 2019-11-26 | 2021-09-16 | 瑞士商諾華公司 | Cd19和cd22嵌合抗原受體及其用途 |
IL296241A (en) | 2020-03-10 | 2022-11-01 | Massachusetts Inst Technology | Compositions and methods for immunotherapy for npm1c-positive cancer |
CA3173527A1 (en) | 2020-03-10 | 2021-09-16 | Massachusetts Institute Of Technology | Methods for generating engineered memory-like nk cells and compositions thereof |
CN111484562B (zh) * | 2020-04-25 | 2021-08-20 | 首都医科大学附属北京朝阳医院 | 一种靶向cd22蛋白的抗体、嵌合抗原受体和药物 |
US20210338833A1 (en) | 2020-05-01 | 2021-11-04 | Massachusetts Institute Of Technology | Chimeric antigen receptor-targeting ligands and uses thereof |
US20210340524A1 (en) | 2020-05-01 | 2021-11-04 | Massachusetts Institute Of Technology | Methods for identifying chimeric antigen receptor-targeting ligands and uses thereof |
CN115515983A (zh) * | 2020-05-06 | 2022-12-23 | 亘喜生物科技(上海)有限公司 | 人源化cd19抗体及其应用 |
CA3189531A1 (en) * | 2020-07-16 | 2022-01-20 | Nanjing Legend Biotech Co., Ltd. | Multispecific chimeric antigen receptors and uses thereof |
WO2022036180A1 (en) | 2020-08-13 | 2022-02-17 | Yale University | Compositions and methods for engineering and selection of car t cells with desired phenotypes |
WO2022109611A1 (en) | 2020-11-20 | 2022-05-27 | Simcere Innovation, Inc. | Armed dual car-t compositions and methods for cancer immunotherapy |
CN116635519A (zh) * | 2020-11-26 | 2023-08-22 | 上海医药集团生物治疗技术有限公司 | 一种经修饰的免疫细胞及其应用 |
US11453723B1 (en) | 2021-06-25 | 2022-09-27 | Mcmaster University | BCMA T cell-antigen couplers and uses thereof |
IL310901A (en) * | 2021-08-18 | 2024-04-01 | Univ Pennsylvania | Compositions and methods for chimeric antigen receptors specific for B cell receptors |
WO2023081715A1 (en) | 2021-11-03 | 2023-05-11 | Viracta Therapeutics, Inc. | Combination of car t-cell therapy with btk inhibitors and methods of use thereof |
CN114133457B (zh) * | 2021-12-08 | 2022-08-19 | 郑州源创吉因实业有限公司 | 一种靶向ror1和cd33的双特异性嵌合抗原受体(car)及其应用 |
WO2023173137A1 (en) | 2022-03-11 | 2023-09-14 | Yale University | Compositions and methods for efficient and stable genetic modification of eukaryotic cells |
Family Cites Families (87)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR901228A (fr) | 1943-01-16 | 1945-07-20 | Deutsche Edelstahlwerke Ag | Système d'aimant à entrefer annulaire |
US4444887A (en) | 1979-12-10 | 1984-04-24 | Sloan-Kettering Institute | Process for making human antibody producing B-lymphocytes |
US4716111A (en) | 1982-08-11 | 1987-12-29 | Trustees Of Boston University | Process for producing human antibodies |
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
US4676980A (en) | 1985-09-23 | 1987-06-30 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Target specific cross-linked heteroantibodies |
US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
GB8607679D0 (en) | 1986-03-27 | 1986-04-30 | Winter G P | Recombinant dna product |
US6548640B1 (en) | 1986-03-27 | 2003-04-15 | Btg International Limited | Altered antibodies |
US5567610A (en) | 1986-09-04 | 1996-10-22 | Bioinvent International Ab | Method of producing human monoclonal antibodies and kit therefor |
US5858358A (en) | 1992-04-07 | 1999-01-12 | The United States Of America As Represented By The Secretary Of The Navy | Methods for selectively stimulating proliferation of T cells |
US6352694B1 (en) | 1994-06-03 | 2002-03-05 | Genetics Institute, Inc. | Methods for inducing a population of T cells to proliferate using agents which recognize TCR/CD3 and ligands which stimulate an accessory molecule on the surface of the T cells |
US6534055B1 (en) | 1988-11-23 | 2003-03-18 | Genetics Institute, Inc. | Methods for selectively stimulating proliferation of T cells |
US6905680B2 (en) | 1988-11-23 | 2005-06-14 | Genetics Institute, Inc. | Methods of treating HIV infected subjects |
US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
US5703055A (en) | 1989-03-21 | 1997-12-30 | Wisconsin Alumni Research Foundation | Generation of antibodies through lipid mediated DNA delivery |
US5399346A (en) | 1989-06-14 | 1995-03-21 | The United States Of America As Represented By The Department Of Health And Human Services | Gene therapy |
US5413923A (en) | 1989-07-25 | 1995-05-09 | Cell Genesys, Inc. | Homologous recombination for universal donor cells and chimeric mammalian hosts |
US5585362A (en) | 1989-08-22 | 1996-12-17 | The Regents Of The University Of Michigan | Adenovirus vectors for gene therapy |
GB8928874D0 (en) | 1989-12-21 | 1990-02-28 | Celltech Ltd | Humanised antibodies |
DK0463151T3 (da) | 1990-01-12 | 1996-07-01 | Cell Genesys Inc | Frembringelse af xenogene antistoffer |
US5229275A (en) | 1990-04-26 | 1993-07-20 | Akzo N.V. | In-vitro method for producing antigen-specific human monoclonal antibodies |
US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
US5814318A (en) | 1990-08-29 | 1998-09-29 | Genpharm International Inc. | Transgenic non-human animals for producing heterologous antibodies |
US5661016A (en) | 1990-08-29 | 1997-08-26 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
US5633425A (en) | 1990-08-29 | 1997-05-27 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
US5625126A (en) | 1990-08-29 | 1997-04-29 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
DK0546073T3 (da) | 1990-08-29 | 1998-02-02 | Genpharm Int | Frembringelse og anvendelse af transgene, ikke-humane dyr, der er i stand til at danne heterologe antistoffer |
EP0519596B1 (en) | 1991-05-17 | 2005-02-23 | Merck & Co. Inc. | A method for reducing the immunogenicity of antibody variable domains |
US5199942A (en) | 1991-06-07 | 1993-04-06 | Immunex Corporation | Method for improving autologous transplantation |
WO1992022653A1 (en) | 1991-06-14 | 1992-12-23 | Genentech, Inc. | Method for making humanized antibodies |
US5565332A (en) | 1991-09-23 | 1996-10-15 | Medical Research Council | Production of chimeric antibodies - a combinatorial approach |
WO1993008829A1 (en) | 1991-11-04 | 1993-05-13 | The Regents Of The University Of California | Compositions that mediate killing of hiv-infected cells |
GB9125768D0 (en) | 1991-12-04 | 1992-02-05 | Hale Geoffrey | Therapeutic method |
ATE249840T1 (de) | 1991-12-13 | 2003-10-15 | Xoma Corp | Verfahren und materialien zur herstellung von modifizierten variablen antikörperdomänen und ihre therapeutische verwendung |
GB9203459D0 (en) | 1992-02-19 | 1992-04-08 | Scotgen Ltd | Antibodies with germ-line variable regions |
US5573905A (en) | 1992-03-30 | 1996-11-12 | The Scripps Research Institute | Encoded combinatorial chemical libraries |
US5504692A (en) | 1992-06-15 | 1996-04-02 | E. I. Du Pont De Nemours Co., Inc. | System and method for improved flow data reconciliation |
US5350674A (en) | 1992-09-04 | 1994-09-27 | Becton, Dickinson And Company | Intrinsic factor - horse peroxidase conjugates and a method for increasing the stability thereof |
US5639641A (en) | 1992-09-09 | 1997-06-17 | Immunogen Inc. | Resurfacing of rodent antibodies |
US5993434A (en) | 1993-04-01 | 1999-11-30 | Genetronics, Inc. | Method of treatment using electroporation mediated delivery of drugs and genes |
US7175843B2 (en) | 1994-06-03 | 2007-02-13 | Genetics Institute, Llc | Methods for selectively stimulating proliferation of T cells |
NZ302513A (en) * | 1995-02-24 | 1999-11-29 | Gen Hospital Corp | Chimeric receptors for redirecting cellular immunity |
US5731168A (en) | 1995-03-01 | 1998-03-24 | Genentech, Inc. | Method for making heteromultimeric polypeptides |
EP0822830B1 (en) | 1995-04-27 | 2008-04-02 | Amgen Fremont Inc. | Human anti-IL-8 antibodies, derived from immunized xenomice |
EP0823941A4 (en) | 1995-04-28 | 2001-09-19 | Abgenix Inc | HUMAN ANTIBODIES DERIVED FROM IMMUNIZED XENO MOUSES |
US6692964B1 (en) | 1995-05-04 | 2004-02-17 | The United States Of America As Represented By The Secretary Of The Navy | Methods for transfecting T cells |
US7067318B2 (en) | 1995-06-07 | 2006-06-27 | The Regents Of The University Of Michigan | Methods for transfecting T cells |
US5916771A (en) | 1996-10-11 | 1999-06-29 | Abgenix, Inc. | Production of a multimeric protein by cell fusion method |
ES2301183T3 (es) | 1996-12-03 | 2008-06-16 | Amgen Fremont Inc. | Anticuerpo completamente humano que se une al receptor del egfr. |
US6261281B1 (en) | 1997-04-03 | 2001-07-17 | Electrofect As | Method for genetic immunization and introduction of molecules into skeletal muscle and immune cells |
RU2224766C2 (ru) | 1997-04-14 | 2004-02-27 | Микромет Аг | Способ получения рецепторов для человеческих антигенов и их применение |
US6235883B1 (en) | 1997-05-05 | 2001-05-22 | Abgenix, Inc. | Human monoclonal antibodies to epidermal growth factor receptor |
US6241701B1 (en) | 1997-08-01 | 2001-06-05 | Genetronics, Inc. | Apparatus for electroporation mediated delivery of drugs and genes |
US6055453A (en) | 1997-08-01 | 2000-04-25 | Genetronics, Inc. | Apparatus for addressing needle array electrodes for electroporation therapy |
US7112324B1 (en) | 1998-04-21 | 2006-09-26 | Micromet Ag | CD 19×CD3 specific polypeptides and uses thereof |
US6678556B1 (en) | 1998-07-13 | 2004-01-13 | Genetronics, Inc. | Electrical field therapy with reduced histopathological change in muscle |
US7171264B1 (en) | 1999-05-10 | 2007-01-30 | Genetronics, Inc. | Intradermal delivery of active agents by needle-free injection and electroporation |
CA2386270A1 (en) | 1999-10-15 | 2001-04-26 | University Of Massachusetts | Rna interference pathway genes as tools for targeted genetic interference |
US6326193B1 (en) | 1999-11-05 | 2001-12-04 | Cambria Biosciences, Llc | Insect control agent |
US6797514B2 (en) | 2000-02-24 | 2004-09-28 | Xcyte Therapies, Inc. | Simultaneous stimulation and concentration of cells |
US7572631B2 (en) | 2000-02-24 | 2009-08-11 | Invitrogen Corporation | Activation and expansion of T cells |
US6867041B2 (en) | 2000-02-24 | 2005-03-15 | Xcyte Therapies, Inc. | Simultaneous stimulation and concentration of cells |
CA2406864A1 (en) | 2000-02-24 | 2001-08-30 | Xcyte Therapies, Inc. | Simultaneous stimulation and concentration of cells |
EP1259265B1 (en) | 2000-03-03 | 2011-06-01 | Genetronics, Inc. | Nucleic acid formulations for gene delivery |
HUP0300369A2 (hu) | 2000-04-11 | 2003-06-28 | Genentech, Inc. | Többértékű antitestek és alkalmazásuk |
AU2001275474A1 (en) | 2000-06-12 | 2001-12-24 | Akkadix Corporation | Materials and methods for the control of nematodes |
CN1195779C (zh) * | 2001-05-24 | 2005-04-06 | 中国科学院遗传与发育生物学研究所 | 抗人卵巢癌抗人cd3双特异性抗体 |
US7745140B2 (en) | 2002-01-03 | 2010-06-29 | The Trustees Of The University Of Pennsylvania | Activation and expansion of T-cells using an engineered multivalent signaling platform as a research tool |
US8209006B2 (en) | 2002-03-07 | 2012-06-26 | Vgx Pharmaceuticals, Inc. | Constant current electroporation device and methods of use |
US20040014645A1 (en) | 2002-05-28 | 2004-01-22 | Advisys, Inc. | Increased delivery of a nucleic acid construct in vivo by the poly-L-glutamate ("PLG") system |
US7328064B2 (en) | 2002-07-04 | 2008-02-05 | Inovio As | Electroporation device and injection apparatus |
US20050070841A1 (en) | 2002-07-04 | 2005-03-31 | Inovio As | Electroporation device and injection apparatus |
CN100509850C (zh) * | 2003-05-31 | 2009-07-08 | 麦克罗梅特股份公司 | 用于治疗b细胞相关疾病的包含双特异性抗cd3、抗cd19抗体构建体的药物组合物 |
AU2004286198C1 (en) | 2003-08-18 | 2011-02-24 | Medimmune, Llc | Humanization of antibodies |
CA2537055A1 (en) | 2003-08-22 | 2005-04-21 | Medimmune, Inc. | Humanization of antibodies |
EP2295588B1 (en) | 2004-05-27 | 2018-03-07 | The Trustees Of The University Of Pennsylvania | Novel artificial antigen presenting cells and uses thefor |
ZA200710496B (en) | 2005-06-02 | 2009-04-29 | Astrazeneca Ab | Antibodies directed to CD20 and used thereof |
CN101370927A (zh) | 2005-12-07 | 2009-02-18 | 基因特伦尼克斯公司 | 可变容积电穿孔室以及其方法 |
PT2066349E (pt) | 2006-09-08 | 2012-07-02 | Medimmune Llc | Anticorpos anti-cd19 humanizados e respectiva utilização no tratamento de tumores, transplantação e doenças auto-imunes |
CL2007003622A1 (es) | 2006-12-13 | 2009-08-07 | Medarex Inc | Anticuerpo monoclonal humano anti-cd19; composicion que lo comprende; y metodo de inhibicion del crecimiento de celulas tumorales. |
EP3663318A1 (en) | 2008-01-07 | 2020-06-10 | Amgen Inc. | Method for making antibody fc-heterodimeric molecules using electrostatic steering effects |
WO2011057124A1 (en) | 2009-11-06 | 2011-05-12 | Transtarget, Inc. | Polyclonal bispecific antibody compositions and method of use |
US9315585B2 (en) * | 2010-06-19 | 2016-04-19 | Memorial Sloan Kettering Cancer Center | Anti-GD2 antibodies |
CA2807278A1 (en) * | 2010-08-24 | 2012-03-01 | F. Hoffmann - La Roche Ag | Bispecific antibodies comprising a disulfide stabilized - fv fragment |
MX347078B (es) | 2010-12-09 | 2017-04-10 | Univ Pennsylvania | Uso de celulas t modificadas por receptor de antigeno quimerico para tratar cancer. |
EP2747781B1 (en) | 2011-08-23 | 2017-11-15 | Roche Glycart AG | Bispecific antibodies specific for t-cell activating antigens and a tumor antigen and methods of use |
EP2814846B1 (en) * | 2012-02-13 | 2020-01-08 | Seattle Children's Hospital d/b/a Seattle Children's Research Institute | Bispecific chimeric antigen receptors and therapeutic uses thereof |
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EA201590208A1 (ru) | 2015-11-30 |
JP2015524255A (ja) | 2015-08-24 |
KR20150029714A (ko) | 2015-03-18 |
BR112015000638A2 (pt) | 2017-08-08 |
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CN104583230A (zh) | 2015-04-29 |
CA2876730A1 (en) | 2014-01-16 |
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SG11201408787PA (en) | 2015-01-29 |
AU2013289971A1 (en) | 2015-01-22 |
EP2872526A2 (en) | 2015-05-20 |
US20210040234A1 (en) | 2021-02-11 |
US20240018271A1 (en) | 2024-01-18 |
EP2872526A4 (en) | 2016-03-23 |
US20150322169A1 (en) | 2015-11-12 |
IL236337A0 (en) | 2015-02-26 |
WO2014011988A3 (en) | 2014-03-13 |
WO2014011988A2 (en) | 2014-01-16 |
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